2-Decarboxy-2-aminomethyl-19-keto-PG compounds

ABSTRACT

The present invention provides novel 2-decarboxy-2-aminomethyl-19-keto-PG compounds, which are useful for a variety of pharmacological purposes, e.g., antiasthmatic indications.

DESCRIPTION CROSS REFERENCE TO RELATED APPLICATION

This application is a division of Ser. No. 025,879, filed Apr. 2, 1979,and now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to novel prostaglandin analogs.Particularly, the invention relates to prostaglandin analogs wherein theC-19 position is substituted by oxo, i.e., 19-keto-PG compounds or19-oxo-PG compounds. Most particularly, the present invention relates tonovel 2-decarboxy-2-aminomethyl-19-keto-PG compounds, a disclosure ofthe preparation and pharmacological use of which is incorporated here byreference from U.S. Pat. No. 4,228,104.

PRIOR ART

Prostaglandins exhibiting a variety of substitution at the C-19 positionare known. See particularly J. C. Sih, et al., JACS 91:3685 (1969)wherein 19-oxo-PGE₂ and 13,14-dihydro-19-oxo-PGE₁ are disclosed.Further, Chemical Abstracts 86:43265H purportedly discloses 19-oxo-PGF₂α. The abstract is derived from Japanese Kokai Pat. No. 76,82,245.

SUMMARY OF THE INVENTION

The present invention particularly provides:

a compound of the formula ##STR1## wherein D is

(1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --,

(2) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --,

(3) cis--CH₂ --CH═CH--CH₂ --CH₂ --,

(4) trans--(CH₂)₃ --CH═CH--,

(5) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,

(6) --(CH₂)₃ --CH₂ --CF₂ --,

(7) --(CH₂)₃ --O--CH₂ --,

(8) --(CH₂)--O--(CH₂)₂ --,

(9) --Ch₂ --O--(CH₂)₃ --,

(10) --(m-Ph)--(Ch₂)₂ --, or

(11) --(m-Ph)--O--Ch₂ --,

wherein --(m--Ph)--is inter-meta-phenylene and

wherein g is zero, one, two, or three;

wherein Q is α--OH:β--R₅ or α--R₅ :β--OH, wherein R₅ is hydrogen ormethyl;

wherein R₇ and R₈ are hydrogen, alkyl of one to 12 carbon atoms,inclusive, benzyl, or phenyl, being the same or different;

wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl,

wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same ordifferent, with the proviso that one of R₃ and R₄ is fluoro only whenthe other is hydrogen or fluoro; and

wherein W is oxo, methylene, α--OH:β--H, or α--H:β--OH; and

wherein X is cis- or trans--CH═CH--, --C.tbd.C--or --Ch₂ CH₂ 13 .

The compounds of the present invention are particularly useful forinducing prostaglandin-like biological effects, as described in UnitedStates Ser. No. 026,066. Uses of compounds in accordance with thepresent invention include, therefore, antiasthmatic indications.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention particularly relates to:

2-decarboxy-2-aminomethyl-19-keto-PGF₂ α.

I claim:
 1. A compound of the formula ##STR2## wherein D is (1)cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g)--CH₂ --, (3) cis--CH₂ --CH═CH--CH₂ --CH₂ --, (4) trans--(CH₂)₃--CH═CH--, (5) --(CH₂)₃ --(CH₂)_(g) --CH₂ --, (6) --(CH₂)₃ --CH₂ --CF₂--, (7) --(CH₂)₃ --O--Ch₂ --, (8) --(CH₂)--O--(CH₂)₂ --, (9) --CH₂--O--(CH₂)₃ --, (10) --(m-Ph)--(CH₂)₂ --, or (11) --(m-Ph)--O--CH₂--,wherein --(m--Ph)--is inter-meta-phenylene and wherein g is zero,one, two, or three; wherein Q is α--OH:β--R₅ or α--R₅ :β--OH, wherein R₅is hydrogen or methyl; wherein R₇ and R₈ are hydrogen, alkyl of one to12 carbon atoms, inclusive, benzyl, or phenyl, being the same ordifferent; wherein R₂ is hydrogen, hydroxyl, or hydroxylmethyl, whereinR₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different,with the proviso that one of R₃ and R₄ is fluoro only when the other ishydrogen or fluoro; and wherein W is oxo, methylene, α--OH:β--H, orα--H:β--OH; and wherein X is cis- or trans--CH═CH--, --C.tbd.C--or --Ch₂CH₂ --.
 2. A compound according to claim 1, wherein D is cis--CH═CH--CH₂--(CH₂)_(g) --CH₂ --.
 3. A compound according to claim 2, wherein W isα--OH:β--H.
 4. A compound according to claim 3, wherein R₂ is hydroxyland X is trans--CH═CH--.
 5. 2-Decarboxy-2-aminomethyl-19-keto-PGF₂ α, acompound according to claim 4.